A variety of sulfated polymers exhibit antiviral activity against human immunodeficiency virus (HIV). Baba et al., Antimicrobial Agents and Chemotherapy, 34(1), 134-138 (1990), discloses using sulfated polyvinyl alcohol, dextran sulfate, or a sulfated copolymer of acrylic acid and vinyl alcohol to inhibit HIV replication and giant cell formation. In similar studies, Mohan et al., Antiviral Research, 18, 139-150 (1992), discloses sulfonic acid polymers, such as poly(4-styrenesulfonic acid), poly(anetholesulfonic acid), poly(vinylsulfonic acid), poly(2-acrylamido-2-methyl-l-propanesulfonic acid), and dextran sulfate, to inhibit HIV and syncytium formation. Other investigators prepared curdlan galactose sulfate, curdlan arabinose sulfate, and lentinan sulfate from respective, nonsulfated polysaccharides. In vitro studies revealed that these sulfated polysaccharides inhibit HIV infection, block cell-fusion events, and inhibit reverse transcriptase (RT) activity (see Yoshida et al., Biochemical Pharmacology, 37(15), 2887-2891 (1988)).
Other investigators (see, for example, Gustafson et al., J. Nat. Can. Inst., 81(16), 1254-1258 (1989), and Ohta et al., Chem. Pharm. Bull., 46(4), 684-686 (1998)) found that certain sulfolipids inhibited the cytopathic effects of the HIV virus and inhibited syncytium formation. However, these sulfolipids are natural products, which are isolated from marine algae using a cumbersome process to yield small amounts of sulfolipid. For example, a relatively large amount of algae (e.g., 300 grams (g) dry weight) is collected, and the sulfolipid is extracted from the algae using organic solvents, then purified. This process provides about 3.1 milligrams (mg) of the purified sulfolipid for an overall yield of 0.0010%. In yet another study, Barzu et al., J. Med. Chem., 36, 3546-3555 (1993), discloses that naturally occurring sulfated polysaccharides, such as heparin, dermatan sulfate, and several chemically modified heparins, inhibited giant-cell formation normally associated with HIV infection.
Accordingly, polymers and polysaccharides having a plurality of sulfur-containing acid groups have demonstrated a positive antiviral effect on HIV in vitro. Harrop et al., Glycobiology, 8(2), 131-137 (1998), explains this behavior by showing that radiolabelled heparin, which is a naturally occurring sulfated polysaccharide, binds to specific glycoproteins on the viral envelope, thereby inhibiting the human immunodeficiency virus from binding to its natural host cell receptor, CD4.
Although the above-discussed sulfated polymers and polysaccharides showed promise in vitro, therapeutic responses in vivo were disappointing. A significant number of the sulfated polymeric materials are not only cost prohibitive, but also exhibit a low efficacy and a low bioavailability in vivo when administered intravenously. The sulfated polymeric materials also demonstrate a strong, undesirable anticoagulant effect. Accordingly, it would be an advance in the art to provide a compound that demonstrates the therapeutic, e.g., antiviral, advantages of sulfated polymeric materials, while overcoming their disadvantages, in the management of AIDS, for example. The present invention is directed to such compounds.